Baculovirus has been used as a vector in methods of industrially producing a desired protein using insect cells. In recent years, it has been found that baculovirus can introduce a foreign gene not only into insect cells but also into mammalian cells, and the possibility of their use as a vector for introducing a therapeutic gene has been found. In Patent document 1, a recombinant baculovirus expression vector having multiple independent promoters composed of a DNA region comprising a gene encoding a viral non-structural protein in the promoter derived from an early gene from the baculovirus and a DNA region comprising a gene encoding a viral structural protein in the promoter derived from a late gene has been disclosed.
In Patent document 2, the method in which a non-mammalian DNA virus comprising a promoter controlled so that an exogenous gene is expressed from a vector in which the desired exogenous genes have been linked to the multiple independent promoters is introduced into a cell and the exogenous gene is expressed in the mammalian cell has been disclosed.
Furthermore, in Patent document 3, the method of producing the protein by gene recombination technology using the baculovirus has been disclosed, and the method of producing the protein by expressing a fusion gene obtained by linking a gp64 gene of the baculovirus to a gene encoding the desired protein, producing the desired protein in a form in which the desired protein has been fused to viral particles, collecting the viral particles fused with the desired protein, and cleaving the desired protein from the viral particles to collect the desired protein has been disclosed.
In Patent document 4, for a baculovirus expression system, a recombinant baculovirus expression vector having multiple independent promoters comprising a first nucleic acid sequence encoding a detection marker linked in the form capable of functioning to a first promoter which is active in a host cell and is inactive in a non-acceptable cell, and a second nucleic acid sequence comprising a foreign nucleic acid sequence linked in the form capable of functioning to a second promoter which is active in the non-acceptable cell has been disclosed.
In patent document 5, it has been disclosed that an influenza virus hemagglutinin (HA) antigen-expressing recombinant baculovirus vector linked to a CAG promoter derived from chicken β actin is useful as a vaccine formulation because the vector has a preventive effect on infection with influenza virus.
In Patent document 6, the method of producing a baculovirus vector comprising a co-transfection step in which a plasmid in which genes encoding proteins expressible on the cell surface have been linked to the baculovirus promoter and the promoter derived from the mammalian cell, respectively, and a plasmid in which genes encoding proteins expressible on the cell surface have been linked to two baculovirus promoters, respectively are co-transfected in the insect cell has been disclosed.
And in patent document 7, a study on an anti-influenza virus activity on the infection with influenza virus using the recombinant baculovirus in which cDNA from influenza virus HA has been incorporated in the CAG promoter has been disclosed, and it has been disclosed that not only the recombinant baculovirus but also a wild type baculovirus has the activity.
This way, in recent years, various recombinant baculoviruses have been developed, and pharmaceutical development for mammals using them has been studied utilizing the recombinant baculovirus as the active ingredient.
In the related art, a recombinant baculovirus vector having a novel structure, and the development of a pharmaceutical formulation, particularly a vaccine formulation using the recombinant baculovirus as the active ingredient, which is effective for infectious diseases such as malaria and influenza, or diseases such as cancer have been desired.
Patent document 1: Japanese Patent No. 3366328, Multiple promoter baculovirus expression system and defect particle products.
Patent document 2: WO98/011243, Non-mammalian DNA virus having modified coating protein.
Patent document 3: JP No. 2002-235236-A, Methods of producing proteins
Patent document 4: JP No. 2003-284557-A, novel baculovirus-transfecting vector and recombinant baculovirus for expression of foreign gene.
Patent document 5: WO02/062381, Baculovirus vector vaccine.
Patent document 6: WO04/029259, Baculovirus vector, method of producing baculovirus vector and method of introducing gene.
Patent document 7: JP No. 2005-15346-A, Baculovirus-containing anti-viral agent.